Over 2,400 people are diagnosed with acute myeloid leukemia (AML) each year in the UK Intensive chemotherapy, followed by a stem cell transplant, currently offering the best chance of a long-term cure.
AML, a highly aggressive form of blood cancer in which immature white blood cells rapidly grow out of control, restricting the production of healthy blood cells. But some people are unable to tolerate this treatment or do not respond, and many more will relapse.
Researchers at the University of Glasgow found that increased activity of a gene called Trib2 was responsible for the development of particular chemotherapy-resistant leukemia cells in around a quarter of AML patients. Trib2 switches on the production of BCL2 proteins, which promotes cell survival and regulate cell death.
When the Researchers added a new targeted drug called venetoclax, Which Inhibits BCL2 protein production, the Trib2-positive leukemia cells Were sensitized to chemotherapy and treatment resistance was overcome.
By switching the Trib2 gene on and off in different types of healthy blood cells grown in the lab, the researchers were able to identify the most likely original blood stem cells from which chemotherapy-resistant Trib2-driven AML develops.
In a blood stem cell called a ' granulocyte-macrophage progenitor ' cell, Trib2 activity led to the development of fast-growing, treatment-resistant leukemia cells in mice. Knowing that it is only these cells that lead to chemoresistance would make it easier for tests to identify chemoresistant cells in patients.
Dr. Karen Keeshan, who led the project at the University of Glasgow, said: "Combining BCL2 inhibitors such as venetoclax with standard chemotherapy appears to be extremely effective at overcoming treatment resistance in this aggressive leukemia in the laboratory.
"A clinical trial is currently underway using venetoclax in combination with low dose chemotherapy to treat older patients with AML. Our findings suggest that testing for diagnosis and relapse could be put in place to identify patients who are most likely to benefit from this targeted treatment, "noted Keeshan.
Dr. Alasdair Rankin, Director of Research at Bloodwise, said: "The outlook for people with AML is currently very poor and new treatments are desperately needed. Fewer than one in five patients will survive for longer than five years after diagnosis, and many are not strong enough to undergo curative treatment."
"Venetoclax is already licensed for use in chronic lymphocytic leukemia, for a group of patients with a specific genetic mutation that indicated they would respond to treatment. These findings suggest that this class of drug could be used similarly for a significant number of patients with AML too, "noted Rankin.
Cliff O'Gorman, Chief Executive of Children with Cancer UK, said: "Aggressive forms of cancer are particularly cruel in children and improving treatment outcomes for young people with AML is very important, especially for those with chemotherapy-resistant cells. "
AML is a form of cancer that affects blood cells called myeloid cells, which include red blood cells, platelets and certain types of white blood cells. Patients experience uncontrolled growth of immature myeloid cells and do not produce enough healthy blood cells.